Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression

In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins β3 and β5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells.

本研究探讨了芍药（Paeonia lactiflora Pall.）提取物在体内外对胚胎着床的调控作用。采用去多糖水提工艺制备的芍药提取物（PL-PP）在非细胞毒性剂量下，可显著上调人子宫内膜Ishikawa细胞中白血病抑制因子(LIF)的表达。PL-PP可显著增强人滋养层外胚层来源的JAr细胞球与子宫内膜Ishikawa细胞的黏附能力。当添加p38激酶抑制剂SB203580与MEK/ERK抑制剂U0126时，PL-PP诱导的LIF表达水平显著降低。进一步实验显示，通过短发夹RNA(shRNA)敲低子宫内膜细胞的LIF表达，可下调整合素β3与β5的表达，并削弱JAr细胞球与Ishikawa细胞的黏附作用。在米非司酮诱导的小鼠胚胎着床障碍模型中，给予PL-PP可恢复小鼠囊胚着床率。本研究结果证实，PL-PP可通过p38与MEK/ERK信号通路上调LIF表达，进而促进滋养层细胞与子宫内膜细胞的黏附。